Journal of Korean Neurosurgical Society

  • 제55권5호
  • /
  • Pages.237-243
  • /
  • 2014
  • /
  • 2005-3711(pISSN)
  • /
  • 1598-7876(eISSN)
대한신경외과학회 (The Korean Neurosurgical Society)
권호 표지
DOI QR코드

DOI QR Code

Matrix Degradative Enzymes and Their Inhibitors during Annular Inflammation : Initial Step of Symptomatic Intervertebral Disc Degeneration

  • Kim, Joo Han (Department of Neurosurgery, Guro Hospital, College of Medicine, Korea University) ;
  • Park, Jin Hyun (Department of Neurosurgery, Guro Hospital, College of Medicine, Korea University) ;
  • Moon, Hong Joo (Department of Neurosurgery, Guro Hospital, College of Medicine, Korea University) ;
  • Kwon, Taek Hyun (Department of Neurosurgery, Guro Hospital, College of Medicine, Korea University) ;
  • Park, Youn Kwan (Department of Neurosurgery, Guro Hospital, College of Medicine, Korea University)
  • 투고 : 2013.12.30
  • 심사 : 2014.05.15
  • 발행 : 2014.05.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective : Symptomatic disc degeneration develops from inflammatory reactions in the annulus fibrosus (AF). Although inflammatory mediators during annular inflammation have been studied, the roles of matrix metalloproteinases (MMPs) and their inhibitors have not been fully elucidated. In this study, we evaluated the production of MMPs and tissue inhibitors of metalloproteinase (TIMPs) during annular inflammation using an in vitro co-culture system. We also examined the effect of notochordal cells on annular inflammation. Methods : Human AF (hAF) pellet was co-cultured for 48 hours with phorbol myristate acetate-stimulated macrophage-like THP-1 cells. hAF pellet and conditioned media (CM) from co-cultured cells were assayed for MMPs, TIMPs, and insulin-like growth factor (IGF)-1 levels using real-time reverse-transcriptase polymerase chain reaction and enzyem-linked immunosorbent assay. To evaluate whether notochordal cells affected MMPs or TIMPs production on annular inflammation, hAF co-cultured with notochordal cells from adult New Zealand White rabbits, were assayed. Results : MMP-1, -3, -9; and TIMP-1 levels were significantly increased in CM of hAF co-cultured with macrophage-like cells compared with hAF alone, whereas TIMP-2 and IGF-1 levels were significantly decreased (p<0.05). After macrophage exposure, hAF produced significantly more MMP-1 and -3 and less TIMP-1 and -2. Interleukin-$1{\beta}$ stimulation enhanced MMP-1 and -3 levels, and significantly diminished TIMP-2 levels. Co-culturing with rabbit notochordal cells did not significantly influence MMPs and TIMPs production or COL1A2 gene expression. Conclusion : Our results indicate that macrophage-like cells evoke annular degeneration through the regulation of major degradative enzymes and their inhibitors, produced by hAF, suggesting that the selective regulation of these enzymes provides future targets for symptomatic disc degeneration therapy.

키워드

참고문헌

  1. Aguiar DJ, Johnson SL, Oegema TR : Notochordal cells interact with nucleus pulposus cells : regulation of proteoglycan synthesis. Exp Cell Res 246 : 129-137, 1999 https://doi.org/10.1006/excr.1998.4287
  2. Andersson GB : Epidemiological features of chronic low-back pain. Lancet 354 : 581-585, 1999 https://doi.org/10.1016/S0140-6736(99)01312-4
  3. Bachmeier BE, Nerlich A, Mittermaier N, Weiler C, Lumenta C, Wuertz K, et al. : Matrix metalloproteinase expression levels suggest distinct enzyme roles during lumbar disc herniation and degeneration. Eur Spine J 18 : 1573-1586, 2009 https://doi.org/10.1007/s00586-009-1031-8
  4. Gomez-Camarillo MA, Almonte-Becerril M, Vasquez Tort M, Tapia-Ramirez J, Kouri Flores JB : Chondrocyte proliferation in a new culture system. Cell Prolif 42 : 207-218, 2009 https://doi.org/10.1111/j.1365-2184.2008.00580.x
  5. Kim JH, Deasy BM, Seo HY, Studer RK, Vo NV, Georgescu HI, et al. : Differentiation of intervertebral notochordal cells through live automated cell imaging system in vitro. Spine (Phila Pa 1976) 34 : 2486-2493, 2009 https://doi.org/10.1097/BRS.0b013e3181b26ed1
  6. Kim JH, Studer RK, Sowa GA, Vo NV, Kang JD : Activated macrophage-like THP-1 cells modulate anulus fibrosus cell production of inflammatory mediators in response to cytokines. Spine (Phila Pa 1976) 33 : 2253-2259, 2008 https://doi.org/10.1097/BRS.0b013e318182c35f
  7. Kjaer M : Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 84 : 649-698, 2004 https://doi.org/10.1152/physrev.00031.2003
  8. Le Maitre CL, Freemont AJ, Hoyland JA : Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J Pathol 204 : 47-54, 2004 https://doi.org/10.1002/path.1608
  9. Masuda K : Biological repair of the degenerated intervertebral disc by the injection of growth factors. Eur Spine J 17 (Suppl 4) : 441-451, 2008 https://doi.org/10.1007/s00586-008-0749-z
  10. Masuda K, Miyabayashi T, Meachum SH, Eurell TE : Proliferation of canine intervertebral disk chondrocytes in three-dimensional alginate microsphere culture. J Vet Med Sci 64 : 79-82, 2002 https://doi.org/10.1292/jvms.64.79
  11. Masuhara K, Nakai T, Yamaguchi K, Yamasaki S, Sasaguri Y : Significant increases in serum and plasma concentrations of matrix metalloproteinases 3 and 9 in patients with rapidly destructive osteoarthritis of the hip. Arthritis Rheum 46 : 2625-2631, 2002 https://doi.org/10.1002/art.10547
  12. Moon HJ, Joe H, Kwon TH, Choi HK, Park YK, Kim JH : Notochordal cells influence gene expression of inflammatory mediators of annulus fibrosus cells in proinflammatory cytokines stimulation. J Korean Neurosurg Soc 48 : 1-7, 2010 https://doi.org/10.3340/jkns.2010.48.1.1
  13. Murphy G, Knauper V, Atkinson S, Butler G, English W, Hutton M, et al. : Matrix metalloproteinases in arthritic disease. Arthritis Res 4 (Suppl 3) : S39-S49, 2002 https://doi.org/10.1186/ar572
  14. Okuma M, Mochida J, Nishimura K, Sakabe K, Seiki K : Reinsertion of stimulated nucleus pulposus cells retards intervertebral disc degeneration : an in vitro and in vivo experimental study. J Orthop Res 18 : 988-997, 2000 https://doi.org/10.1002/jor.1100180620
  15. Peng B, Hao J, Hou S, Wu W, Jiang D, Fu X, et al. : Possible pathogenesis of painful intervertebral disc degeneration. Spine (Phila Pa 1976) 31 : 560-566, 2006 https://doi.org/10.1097/01.brs.0000201324.45537.46
  16. Peng B, Wu W, Hou S, Li P, Zhang C, Yang Y : The pathogenesis of discogenic low back pain. J Bone Joint Surg Br 87 : 62-67, 2005
  17. Roberts S, Caterson B, Menage J, Evans EH, Jaffray DC, Eisenstein SM : Matrix metalloproteinases and aggrecanase : their role in disorders of the human intervertebral disc. Spine (Phila Pa 1976) 25 : 3005-3013, 2000 https://doi.org/10.1097/00007632-200012010-00007
  18. Roughley PJ : Biology of intervertebral disc aging and degeneration : involvement of the extracellular matrix. Spine (Phila Pa 1976) 29 : 2691-2699, 2004 https://doi.org/10.1097/01.brs.0000146101.53784.b1
  19. Stetler-Stevenson WG, Seo DW : TIMP-2 : an endogenous inhibitor of angiogenesis. Trends Mol Med 11 : 97-103, 2005 https://doi.org/10.1016/j.molmed.2005.01.007
  20. Tsuchiya S, Kobayashi Y, Goto Y, Okumura H, Nakae S, Konno T, et al. : Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res 42 : 1530-1536, 1982
  21. Walmsley R : The development and growth of the intervertebral disc. Edinb Med J 60 : 341-364, 1953
  22. Weiler C, Nerlich AG, Zipperer J, Bachmeier BE, Boos N : 2002 SSE Award Competition in Basic Science : expression of major matrix metalloproteinases is associated with intervertebral disc degradation and resorption. Eur Spine J 11 : 308-320, 2002 https://doi.org/10.1007/s00586-002-0472-0

피인용 문헌

  1. IL‐1β‐regulating angiogenic factors expression in perforated temporomandibular disk cells via NF‐κB pathway vol.45, pp.8, 2014, https://doi.org/10.1111/jop.12420
  2. Immunobiology of periprosthetic inflammation and pain following ultra-high-molecular-weight-polyethylene wear debris in the lumbar spine vol.14, pp.8, 2014, https://doi.org/10.1080/1744666x.2018.1511428
  3. Increased lactic acid content associated with extracellular matrix depletion in a porcine disc degeneration induced by superficial annular lesion vol.20, pp.1, 2014, https://doi.org/10.1186/s12891-019-2937-x